Retinopathy is typically a non-inflammatory degenerative disease of the retina that may lead to visual field loss or blindness. Retinopathy can be caused by various ophthalmic conditions as well as numerous systemic diseases outside the eye, for example diabetes. Diabetic retinopathy is an eye disease that results from damage to the retina as a result of complications such as nerve damage arising from diabetes mellitus. Diabetic retinopathy affects more than 80% of all patients who have had diabetes for 10 years or more and is the leading cause of vision loss in developed countries (Aiello et al., 1998).
Many retinal disorders can be diagnosed with the aid of retinal examination. Fundus photography is a common method of determining the presence and extent of diabetic retinopathy (Wilkinson, et al. 2003). Laser photocoagulation, which has been applied in DR treatment for over half a century (Antonetti et al., 2006), is a common treatment. Laser photocoagulation is successful in arresting proliferative diabetic retinopathy (PDR) in 50% of cases. Even where further degeneration is prevented, any vision loss already incurred cannot be restored (Schwartz and Flynn, 2007).
Pupillary light reflex (PLR) refers to the dilation/constriction of the pupil in response to light reaching the retina. High intensity light on the retina results in constriction in order to reduce the total light reaching the retina, and conversely, low intensity light results in pupil dilation in order to increase the light entering the eye and reaching the retina. PLR can provide a useful diagnostic tool, allowing for testing of the sensory and motor responses of the eye. Lesions or disruptions in the eye can be detected by testing the direct response of a particular eye exposed to light entering the pupil as well as the consensual response of the eye when the opposite eye is exposed to light entering the pupil.
PLR has conventionally been used in the clinical setting to characterize the early effects of diabetic neuropathy (Hreidarsson, 1982; Devos et al., 1989; Kuroda et al., 1989). Such methods involve direct measurement of the pupil diameter or area in response to intense light. These methods, however do not change the illumination based on the pupil size and therefore provide a retinal stimulation that varies with pupil size.
Visual electrophysiology diagnostic tests such as the electroretinogram (ERG) and visual evoked potentials (VEP) are diagnostic tests used to help assess eye disease. See, for example, the textbook Principles and Practice of Clinical Electrophysiology of Vision, 2nd edition, edited by Heckenlively and Arden (2006), which describes dozens of diseases that can be diagnosed with the aid of visual electrophysiology. Standards have been developed for the most common of these tests, as described in Marmor et al. (2009), Hood et al. (2012), Holder et al. (2007), and Odom et al. (2010). As a specific example, some features of the clinical ERG are strongly correlated with diabetic retinopathy (Bresnick and Palta, 1987), (Han and Ohn, 2000) and (Satoh et al., 1994). As another example, Kjeka et al. (2013) showed greatly improved outcomes for the treatment of central retinal vein occlusion when basing treatment decisions on ERG results rather than ophthalmologic examinations alone.
Normally, ERG measurements are recorded using a large instrument (e.g., the LKC Technologies UTAS system) in a darkened room with electrodes placed directly onto the eye. Dilating drops are used to enlarge the pupil and anesthetic drops are used to numb the eye before placing the electrodes onto the eye. The eye is stimulated with light to elicit a response from the visual system which is recorded via the electrodes. The measurements are performed by a skilled technician, and the results are usually interpreted by an ophthalmologist or PhD expert in visual electrophysiology. The invasiveness and complexity described above have prevented the ERG from having widespread use in assessing diabetic retinopathy and other diseases.
The invention described in U.S. Pat. No. 7,540,613 and U.S. patent application 61/757,316, which are herein incorporated by reference, help prevent these disadvantages with ERG measurements. Nevertheless, there still exists a need for visual electrophysiology devices that are easier to use or have improved performance.
While ERG measurements have been used to assess eye disease, the combination of PLR and ERG has not been contemplated previously as a way to improve assessment of eye disease.
Effective detection and treatment of retinopathy, including diabetic retinopathy would help to minimize vision loss in affected patients.